tbuckley/cabot-search huggingface dataset:
Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline
Authors: David Schiff, Hans Messersmith, Priscilla K. Brastianos, Paul D. Brown, Stuart Burri, Ian F. Dunn, Laurie E. Gaspar, Vinai Gondi, Justin T. Jordan, Julia Maues, Nimish Mohile, Navid Redjal, Glen H.J. Stevens, Erik P. Sulman, Martin van den Bent, H. James Wallace, Gelareh Zadeh, Michael A. Vogelbaum
Journal: Journal of Clinical Oncology (2022)

American Society of Radiation Oncology (ASTRO) has developed a guideline on appropriate radiation therapy for brain metastases. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations."Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline"2 was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations.The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline, published May 6, 2022, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorses "Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline."2.Within the guideline, stereotactic radiosurgery (SRS) is recommended for patients with Eastern Cooperative Oncology Group performance status of 0-2 and up to four intact brain metastases, and conditionally recommended for patients with up to 10 intact brain metastases. The guideline provides detailed dosing and fractionation recommendations on the basis of the size of the metastases. For patients with resected brain metastases, radiation therapy (SRS or whole-brain radiation therapy [WBRT]) is recommended to improve intracranial disease control; if there are limited additional brain metastases, SRS is recommended over WBRT. For patients with favorable prognosis and brain metastases ineligible for surgery and/or SRS, WBRT is recommended with hippocampal avoidance where possible and the addition of memantine is recommended. For patients with brain metastases, limiting the single-fraction V12Gy to brain tissue to ≤ 10 cm3 is conditionally recommended.Additional information is available at www.asco.org/neurooncology-guidelines.
Abstract A012: Advanced melanoma exhibits a diversity of evolutionary routes to lethality
Authors: Alexander Coulton, Irene Lobon, Lavinia Spain, Andrew Rowan, Desiree Shnidrig, Scott Shepherd, Ben Shum, Fiona Byrne, Lewis Au, Kim Edmonds, Ellie Carlyle, Alexandra Renn, Christina Messiou, Charlotte Spencer, Andreas M. Schmidt, Zayd Tippu, Aljosja Rogiers, Max Emmerich, Camille Gerard, Husayn Pallikonda, Cristina Naceur-Lombardelli, Floris Foijer, Hilda van den Bos, René Wardenaar, Diana Spierings, Kate Young, Lisa Pickering, Andrew Furness, Elaine Borg, Miriam Mitchison, David Moore, Mary Falzon, Ian Proctor, Ruby Stewart, Ula Mahadeva, Anna Green, James Larkin, Charles Swanton, Mariam Jamal-Hanjani, Kevin Litchfield, Samra Turajlic
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR002) of the Conference Proceedings. Citation Format: Alexander Coulton, Irene Lobon, Lavinia Spain, Andrew Rowan, Desiree Shnidrig, Scott Shepherd, Ben Shum, Fiona Byrne, Lewis Au, Kim Edmonds, Ellie Carlyle, Alexandra Renn, Christina Messiou, Charlotte Spencer, Andreas M. Schmidt, Zayd Tippu, Aljosja Rogiers, Max Emmerich, Camille Gerard, Husayn Pallikonda, Cristina Naceur-Lombardelli, Floris Foijer, Hilda van den Bos, René Wardenaar, Diana Spierings, Kate Young, Lisa Pickering, Andrew Furness, Elaine Borg, Miriam Mitchison, David Moore, Mary Falzon, Ian Proctor, Ruby Stewart, Ula Mahadeva, Anna Green, James Larkin, Charles Swanton, Mariam Jamal-Hanjani, Kevin Litchfield, Samra Turajlic. Advanced melanoma exhibits a diversity of evolutionary routes to lethality [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A012.
A Multicenter Weighted Lottery to Equitably Allocate Scarce COVID-19 Therapeutics
Authors: Douglas B. White, Erin K. McCreary, Chung-Chou H. Chang, Mark Schmidhofer, J. Ryan Bariola, Naudia N. Jonassaint, Govind Persad, Robert D. Truog, Parag Pathak, Tayfun Sonmez, M. Utku Unver
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
Final Results of Neoadjuvant Atezolizumab in Cisplatin-ineligible Patients with Muscle-invasive Urothelial Cancer of the Bladder
Authors: Bernadett Szabados, Mark Kockx, Zoe June Assaf, Pieter-Jan van Dam, Alejo Rodriguez-Vida, Ignacio Duran, Simon J. Crabb, Michiel S. Van Der Heijden, Albert Font Pous, Gwenaelle Gravis, Urbano Anido Herranz, Andrew Protheroe, Alain Ravaud, Denis Maillet, Maria Jose Mendez, Cristina Suarez, Mark Linch, Aaron Prendergast, Charlotte Tyson, Diana Stanoeva, Sofie Daelemans, Miche Rombouts, Sanjeev Mariathasan, Joy S. Tea, Kelly Mousa, Shruti Sharma, Alexey Aleshin, Romain Banchereau, Daniel Castellano, Thomas Powles
Journal: European Urology (2022)
Perspectives on Use of the Cutaneous Direct Immunofluorescence Assay
Authors: Julia S. Lehman, Donna A. Culton, Alina G. Bridges
Journal: JAMA Dermatology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Efficient antibody evasion but reduced ACE2 binding by the emerging SARS-CoV-2 variant B.1.640.2
Authors: Prerna Arora, Amy Kempf, Inga Nehlmeier, Luise Graichen, Sebastian Schulz, Anne Cossmann, Alexandra Dopfer-Jablonka, Martin S. Winkler, Hans-Martin Jäck, Georg M. N. Behrens, Stefan Pöhlmann, Markus Hoffmann
Journal: Cellular and Molecular Immunology (2022)

The SARS-CoV-2 spike (S) protein engages ACE2 for cell entry, and the S protein/ACE2 interface is an important target for neutralizing antibodies.In the course of the COVID-19 pandemic, SARS-CoV-2 variants have emerged that harbor mutations in the S protein, which confer neutralization resistance and allow viral spread in immunologically nonnaive populations.The most prominent example is the highly mutated Omicron variant, which infects convalescent or vaccinated individuals with unprecedented efficiency [1, 2], highlighting the threat that emerging SARS-CoV-2 variants pose to efforts to control the pandemic.Recently, a novel SARS-CoV-2 variant, B.1.640.2, which harbors an unusually high number of mutations in the S protein, was detected in southern France [3].Here, we analyzed the impact of these mutations on viral cell tropism, ACE2 interactions, and antibodymediated neutralization.The B.1.640.2 variant was detected in November 2021 in a vaccinated adult patient who had returned from Cameroon and exhibited mild respiratory symptoms [3].B.1.640.2 infection was also detected in 12 other individuals living in the same area [3].The B.1.640.2 S protein analyzed in the present study harbors 13 amino acid substitutions and two deletions (Fig. 1a,b).Three amino acid substitutions and two deletions are located in the N-terminal domain of the S protein (Fig. 1a,b), while six amino acid substitutions are found in the receptor-binding domain (RBD), the portion of the S protein that binds to ACE2 (Fig. 1a,b).While some of these mutations likely alter epitopes for neutralizing antibodies, the Y449N substitution in the RBD is known to impair ACE2 binding [4].For analysis of the B.1.640.2 S protein, we employed rhabdoviral pseudotypes, which faithfully mimic SARS-CoV-2 entry and antibody-mediated neutralization [5].We first asked whether particles pseudotyped with B.1.640.2 S protein (B.1.640.2 pp ) can enter cell lines commonly used for SARS-CoV-2 research.The S proteins of variant B.1, which circulated early in the pandemic, and the Omicron variant (sublineage BA.1) served as controls.All particles entered Huh-7 (human liver) and Vero cells (African green monkey kidney) robustly and at comparable rates, and entry efficiency was not increased by the expression of TMPRSS2, an S protein-activating host cell protease (Fig. 1c).Furthermore,
Sex Disparities in Trauma Care—Why Are the Women Waiting?
Authors: Rachel L. Warner, Marie Crandall
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Flexible 3D Nanonetworked Silica Film as a Polymer‐Free Drug‐Eluting Stent Platform to Effectively Suppress Tissue Hyperplasia in Rat Esophagus
Authors: Eunyoung Jeon, Jeon Min Kang, Ga‐Hyun Bae, Chu Hui Zeng, Seungyong Shin, Byeongdu Lee, Wooram Park, Jung‐Hoon Park, Joonseok Lee
Journal: Advanced Healthcare Materials (2022)

Loading and eluting drugs on self-expandable metallic stents (SEMSs) can be challenging in terms of fabrication, mechanical stability, and therapeutic effects. In this study, a flexible 3D nanonetworked silica film (NSF) capable of withstanding mechanical stress during dynamic expansion is constructed to function as a drug delivery platform on an entire SEMS surface. Despite covering a broad curved area, the synthesized NSF is defect-free and thin enough to increase the stent strut diameter (110 µm) by only 0.4 percent (110.45 µm). The hydrophobic modification of the surface enables loading of 4.7 times the sirolimus (SRL) concentration in NSF than Cypher, polymer-coated commercial stent, which is based on the same thickness of coating layer. Furthermore, SRL-loaded NSF exhibits a twofold delay in release compared to the control group without NSF. The SRL-loaded NSF SEMS significantly suppresses stent-induced tissue hyperplasia than the control SEMS in the rat esophagus (all variables, p < 0.05). Thus, the developed NSF is a promising polymer-free drug delivery platform to efficiently treat esophageal stricture.
Nonalcoholic fatty liver disease and accelerated loss of skeletal muscle mass: A longitudinal cohort study
Authors: Dong Hyun Sinn, Danbee Kang, Mira Kang, Eliseo Guallar, Yun Soo Hong, Kyung Hyun Lee, Jiyeon Park, Juhee Cho, Geum‐Youn Gwak
Journal: Hepatology (2022)

Whether subjects with NAFLD are at increased risk of sarcopenia is not well established.This is a cohort study of 52,815 men and women of 20 years of age or older who underwent at least two health check-up exams with bioelectrical impedance analysis and abdominal ultrasound imaging. Bioelectrical impedance analysis was used to calculate appendicular skeletal muscle mass (ASM). NAFLD was assessed by ultrasonography, and its severity was assessed by the NAFLD fibrosis score (NFS). We estimated the 5-year change in ASM comparing participants with and without NAFLD at baseline using mixed linear models. The 5-year change in ASM in participants without and with NAFLD was -225.2 g (95% CI -232.3, -218.0) and -281.3 g (95% CI -292.0, -270.6), respectively (p < 0.001). In multivariable adjusted analysis, the difference in 5-year change in ASM comparing participants with and without NAFLD was -39.9 g (95% CI -53.1, -26.8). When participants with NAFLD were further divided by NAFLD severity, ASM loss was much faster in participants with NAFLD with intermediate to high NFS than in those with low NFS.Participants with NAFLD were at increased risk of sarcopenia, indicated by faster loss of skeletal muscle mass. Patients with NAFLD may need screening and early intervention to mitigate skeletal muscle mass loss.
Tubular IL-1β Induces Salt Sensitivity in Diabetes by Activating Renal Macrophages
Authors: Luciana C. Veiras, Ellen A. Bernstein, DuoYao Cao, Derick Okwan-Duodu, Zakir Khan, David R. Gibb, Arantxa Roach, Rachel Skelton, Ryan M. Williams, Kenneth E. Bernstein, Jorge F. Giani
Journal: Circulation Research (2022)

Chronic renal inflammation has been widely recognized as a major promoter of several forms of high blood pressure including salt-sensitive hypertension. In diabetes, IL (interleukin)-6 induces salt sensitivity through a dysregulation of the epithelial sodium channel. However, the origin of this inflammatory process and the molecular events that culminates with an abnormal regulation of epithelial sodium channel and salt sensitivity in diabetes are largely unknown.Both in vitro and in vivo approaches were used to investigate the molecular and cellular contributors to the renal inflammation associated with diabetic kidney disease and how these inflammatory components interact to develop salt sensitivity in db/db mice.Thirty-four-week-old db/db mice display significantly higher levels of IL-1β in renal tubules compared with nondiabetic db/+ mice. Specific suppression of IL-1β in renal tubules prevented salt sensitivity in db/db mice. A primary culture of renal tubular epithelial cells from wild-type mice releases significant levels of IL-1β when exposed to a high glucose environment. Coculture of tubular epithelial cells and bone marrow-derived macrophages revealed that tubular epithelial cell-derived IL-1β promotes the polarization of macrophages towards a proinflammatory phenotype resulting in IL-6 secretion. To evaluate whether macrophages are the cellular target of IL-1β in vivo, diabetic db/db mice were transplanted with the bone marrow of IL-1R1 (IL-1 receptor type 1) knockout mice. db/db mice harboring an IL-1 receptor type 1 knockout bone marrow remained salt resistant, display lower renal inflammation and lower expression and activity of epithelial sodium channel compared with db/db transplanted with a wild-type bone marrow.Renal tubular epithelial cell-derived IL-1β polarizes renal macrophages towards a proinflammatory phenotype that promotes salt sensitivity through the accumulation of renal IL-6. When tubular IL-1β synthesis is suppressed or in db/db mice in which immune cells lack the IL-1R1, macrophage polarization is blunted resulting in no salt-sensitive hypertension.
Importance of Genotyping in von Willebrand Disease to Elucidate Pathogenic Mechanisms and Variability in Phenotype
Authors: Ferdows Atiq, Johan Boender, Waander L. van Heerde, Juan M. Tellez Garcia, Selene C. Schoormans, Sandy Krouwel, Marjon H. Cnossen, Britta A. P. Laros-van Gorkom, Joke de Meris, Karin Fijnvandraat, Johanna G. van der Bom, Karina Meijer, Karin P. M. van Galen, Jeroen Eikenboom, Frank W. G. Leebeek
Journal: HemaSphere (2022)

Genotyping is not routinely performed at diagnosis of von Willebrand disease (VWD). Therefore, the association between genetic variants and pathogenic mechanism or the clinical and laboratory phenotype is unknown in most patients, especially in type 1 VWD. To investigate whether genotyping adds to a better understanding of the pathogenic mechanisms and variability in phenotype, we analyzed the VWF gene in 390 well-defined VWD patients, included in the WiN study. A VWF gene variant was found in 155 patients (61.5%) with type 1, 122 patients (98.4%) with type 2, and 14 patients (100%) with type 3 VWD. Forty-eight variants were novel. For each VWF gene variant, the pathogenic mechanisms associated with reduced VWF levels was investigated using the FVIII:C/VWF:Ag and VWFpp/VWF:Ag ratios. In type 1 VWD, reduced synthesis or secretion of VWF was most frequently found in patients with nonsense variants, frameshift variants, and deletions, whereas rapid clearance of VWF was mainly found in patients with missense variants. Furthermore, type 1 VWD patients with and without a VWF gene variant were clearly distinct in their clinical features such as age of diagnosis, laboratory phenotype, and bleeding phenotype. In type 2 VWD, 81% of variants were associated with an increased clearance of VWF. To conclude, we identified the pathogenic mechanisms associated with various VWF gene variants in type 1, 2, and 3 VWD patients. Additionally, major differences in the phenotype of type 1 VWD patients with and without a variant were observed, which may be of importance for clinical management.
Lenacapavir for HIV-1 — Potential Promise of a Long-Acting Antiretroviral Drug
Authors: Jeanne Marrazzo
Journal: New England Journal of Medicine (2022)

As we walk through the lobby of a modern clinic for the treatment of patients with human immunodeficiency virus (HIV) infection or review antiretroviral regimens in the electronic medical record, it is easy to forget the days when managing multidrug-resistant HIV-1 was routine. Although the advent of protease inhibitors has saved lives,1 many patients already had resistance mutations to then-available nucleoside reverse-transcriptase inhibitors (NRTIs). For these patients and for others who contracted HIV infection with primary resistance, the subsequent iterative availability of new drug classes, including non-NRTIs and integrase-strand transferase inhibitors, essentially offered functional monotherapy against a background of complex . . .
The Origins, Evolution, and Future of Dietary Methionine Restriction
Authors: Han Fang, Kirsten P. Stone, Desiree Wanders, Laura A. Forney, Thomas W. Gettys
Journal: Annual Review of Nutrition (2022)

The original description of dietary methionine restriction (MR) used semipurified diets to limit methionine intake to 20% of normal levels, and this reduction in dietary methionine increased longevity by ∼30% in rats. The MR diet also produces paradoxical increases in energy intake and expenditure and limits fat deposition while reducing tissue and circulating lipids and enhancing overall insulin sensitivity. In the years following the original 1993 report, a comprehensive effort has been made to understand the nutrient sensing and signaling systems linking reduced dietary methionine to the behavioral, physiological, biochemical, and transcriptional components of the response. Recent work has shown that transcriptional activation of hepatic fibroblast growth factor 21 (FGF21) is a key event linking the MR diet to many but not all components of its metabolic phenotype. These findings raise the interesting possibility of developing therapeutic, MR-based diets that produce the beneficial effects of FGF21 by nutritionally modulating its transcription and release.
AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or MetastaticNon–Small-Cell Lung Cancer With <i>EGFR</i> Exon 19 Deletion or L858R Mutations
Authors: Shun Lu, Xiaorong Dong, Hong Jian, Jianhua Chen, Gongyan Chen, Yuping Sun, Yinghua Ji, Ziping Wang, Jianhua Shi, Junguo Lu, Shaoshui Chen, Dongqing Lv, Guojun Zhang, Chunling Liu, Juan Li, Xinmin Yu, Zhong Lin, Zhuang Yu, Zhehai Wang, Jiuwei Cui, Xingxiang Xu, Jian Fang, Jifeng Feng, Zhi Xu, Rui Ma, Jie Hu, Nong Yang, Xiangdong Zhou, Xiaohong Wu, Chengping Hu, Zhihong Zhang, You Lu, Yanping Hu, Liyan Jiang, Qiming Wang, Renhua Guo, Jianying Zhou, Baolan Li, Chunhong Hu, Wancheng Tong, Helong Zhang, Lin Ma, Yuan Chen, Zhijun Jie, Yu Yao, Longzhen Zhang, Weng Jie, Weidong Li, Jianping Xiong, Xianwei Ye, Jianchun Duan, Haihua Yang, Meili Sun, Changan Sun, Hongying Wei, Chuan Li, Siraj M. Ali, Vincent A. Miller, Qiong Wu
Journal: Journal of Clinical Oncology (2022)

Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non-small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768).Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment.A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P < .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively.Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.